TMCH is a spontaneous disease of mice characterized by mucosal hyperplasia with minimal inflammatory change. As in colon carcinogenesis, TMCH is dependent upon the interaction of gut microflora, host genetics, and diet. The kinetics of TMCH resemble changes seen in preneoplastic and neoplastic lesions of the colon. Because of the intimate association of hyperplasia with colonic neoplasia, TMCH offers an opportunity to study the interaction of hyperplasia with carcinogenesis. It has been shown that TMCH promotes large bowel chemical carcinogenesis by reducing the latent period and increasing the sensitivity of the mucosa to low doses of carcinogen. The proposed studies will utilize TMCH as a model of colon tumor promotion, seeking to determine the influencing mechanisms of hyperplasia on neoplasia as well as understand the pathogenesis of mucosal proliferation. Proposed studies will include investigations into mucosal repair of carcinogen damage, initiation and promotion in large bowel carcinogenesis, early colonic neoplasia, nutritional and bacterial mechanisms in TMCH, role of genetics in TMCH and colonic carcinogenesis, and changes in composition of mucosal antigens and histochemistry of colon mucosubstances in hyperplasia.